2,687 research outputs found
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Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.
Acetaminophen (APAP)-induced liver injury is clinically significant, and APAP overdose in mice often serves as a model for drug-induced liver injury in humans. By specifying that APAP metabolism, reactive metabolite formation, glutathione depletion, and mitigation of mitochondrial damage within individual hepatocytes are functions of intralobular location, an earlier virtual model mechanism provided the first concrete multiattribute explanation for how and why early necrosis occurs close to the central vein (CV). However, two characteristic features could not be simulated consistently: necrosis occurring first adjacent to the CV, and subsequent necrosis occurring primarily adjacent to hepatocytes that have already initiated necrosis. We sought parsimonious model mechanism enhancements that would manage spatiotemporal heterogeneity sufficiently to enable meeting two new target attributes and conducted virtual experiments to explore different ideas for model mechanism improvement at intrahepatocyte and multihepatocyte levels. For the latter, evidence supports intercellular communication via exosomes, gap junctions, and connexin hemichannels playing essential roles in the toxic effects of chemicals, including facilitating or counteracting cell death processes. Logic requiring hepatocytes to obtain current information about whether downstream and lateral neighbors have triggered necrosis enabled virtual hepatocytes to achieve both new target attributes. A virtual hepatocyte that is glutathione-depleted uses that information to determine if it will initiate necrosis. When a less-stressed hepatocyte is flanked by at least two neighbors that have triggered necrosis, it too will initiate necrosis. We hypothesize that the resulting intercellular communication-enabled model mechanism is analogous to the actual explanation for APAP-induced hepatotoxicity at comparable levels of granularity
Combinatorial biomaterials discovery strategy to identify new macromolecular cryoprotectants
Cryoprotective agents (CPAs) are typically solvents or small molecules, but there is a need for innovative CPAs to reduce toxicity and increase cell yield, for the banking and transport of cells. Here we use a photochemical high-throughput discovery platform to identify macromolecular cryoprotectants, as rational design approaches are currently limited by the lack of structureāproperty relationships. Using liquid handling systems, 120 unique polyampholytes were synthesized using photopolymerization with RAFT agents. Cryopreservation screening identified āhitā polymers and nonlinear trends between composition and function, highlighting the requirement for screening, with polymer aggregation being a key factor. The most active polymers reduced the volume of dimethyl sulfoxide (DMSO) required to cryopreserve a nucleated cell line, demonstrating the potential of this approach to identify materials for cell storage and transport
Tuning Photocurrent Responses from Photosystem I via Microenvironment Alterations: Effect of Plasmonic Electric Fields and Membrane Confinements
Robust photoelectrochemical activities of PSI make it an ideal candidate for bio-hybrid photovoltaic and optoelectronic devices. This dissertation focuses on role of microenvironment alterations around PSI in tuning its photocurrent responses when assembled with tailored plasmonic metal nanostructures and biomimetic lipid interfaces. To this end, a series of systematic studies aimed at tuning the plasmon enhanced photocurrent responses from PSI assembled with gold and silver metal nanopatterns tailored for different plasmonic absorption wavelengths. The experimental observation of plasmon-induced photocurrent enhancements in PSI is investigated using Fischer patterns of silver nanopyramids (Ag-NPs) wherein the resonant peaks were tuned to match the PSI absorption peaks at ~450 and ~680 nm. A conservative estimate for the enhancement factors were found to be ~ 5.8 ā 6.5 when compared to PSI on planar Ag substrate assemblies. Furthermore, spatially localized and spectrally resolved wavelength-dependent plasmon-enhanced photocurrents from PSI are investigated by specifically assembling the protein units in regions around highly ordered Au (AuND) and Ag (AgND) nano-discs where the dipolar plasmon resonance modes from the respective NDs are tuned to the wavelengths of ~680 nm and ~560 nm, respectively. Specifically, we report plasmon-enhancement factors of ~6.8 and ~17.5 for the PSI photocurrents recorded under the excitation wavelengths of ~680 nm and ~565 nm respectively as compared to PSI assembled on planar ITO substrates. The results indicate: 1) direct correlations between the photocurrent enhancement spectra from the PSI assemblies and the plasmonic resonance modes for the respective nanopatterned substrates, and 2) broadband photocurrent enhancements due to plasmon-coupled photoactivation in the otherwise blind chlorophyll regions of the native PSI absorption spectra. In our continuing efforts to investigate the alterations in the photoexcitation/dissipation pathways in PSI due to characteristic changes in their optical and structural properties under biomimetic membrane confinements, , the PSI complexes are reconstituted in synthetic lipid membranes of 1,2-diphytanoyl-sn-glycero-3-phospho-(1Ź¹-rac-glycerol) (DPhPG) and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC). The results presented here from absorption, fluorescence and circular dichroism indicate unique changes around the carotenoid/chlorophyll spectral bands leading to attainment of broad-band light harvesting via enhanced absorption in the otherwise non-absorptive green region (500 ā 580 nm) of unconfined PSI absorption spectra
Morphological and Photoelectrochemical Characterization of Membrane Reconstituted Photosystem I (PSI)
The robust structural and photoactive electrochemical properties of Photosystem I (PSI), a transmembrane photosynthetic protein complex, make it an ideal candidate for incorporation into solid state bioelectronic or hybrid photovoltaic devices. However, the first step towards the successful fabrication of such devices requires systematic assembly of oriented and functional PSI onto desired bio-abio interfaces via suitable protein scaffoldings. Hence, this dissertation focuses on utilizing the cyanobacterial PSI for integration into organic/inorganic interfaces that mediate photo-electrochemical energy conversions for electricity and/or solar fuel production. To this end, in this study the effect of systematic incorporation of PSI complexes into synthetic membrane-bound structures that mimic the natural thylakoid membrane housing of PSI quantifies via its performance and photocurrent response is demonstrated. Therefore, the surfactant-induced membrane solubilization of three phospholipids, namely DPhPC (1,2-diphytanoyl-sn-glycero-3-phosphocholine), DPPG (1,2-dipalmitoyl-sn-glycero-3-phospho-(1\u27-rac-glycerol)), and DPhPG (1,2-diphytanoyl-sn-glycero-3-phospho-(1\u27-rac-glycerol)) with the motivation of creating biomimetic reconstructs of PSI reconstitution in these liposomes are studied via isothermal titration calorimetry, turbidity measurements, dynamic light scattering and cryo-transmission electron microscopy imaging. The results indicate the typical three-stage solubilization process during lamellar-to-micellar transitions for liposomes is dictated by the critical detergent/phospholipid ratios. Considering that most successful protein incorporation occurs during the second stage of solublization, these studies set the backdrop for ideal concentration ratios for successful protein insertion in this stage. Furthermore, a facile yet elegant method for incorporation of PSI trimeric complexes into DPhPG bilayer membranes is introduced. The efficacy of this method is demonstrated via absorption and fluorescence spectroscopy measurements as well as direct visualization using atomic force microscopy. This study also provides direct evidence that PSI confinements in synthetic lipid scaffolds can be used for tuning the photoexcitation characteristics of PSI. Finally, detailed chronoamperometry measurements were conducted on PSI-proteoliposomes made from PSI incorporated within biomimetic membrane scaffolds and supported on suitable SAM substrates to investigate the enhancement in photocurrent responses arising from such confinement. The significant observation here is that the photo currents generated from PSI complexes under liposome confinements produce photocurrents four times higher than that produced from dense monolayer of individual PSI on SAM substrates using an equivalent concentration of PSI
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Leaf-inspired microcontact printing vascular patterns.
The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cellsĀ that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 Ī¼g ml-1 of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues
Polarization control of metal-enhanced fluorescence in hybrid assemblies of photosynthetic complexes and gold nanorods
Fluorescence imaging of hybrid nanostructures composed of a bacterial light-harvesting complex LH2 and Au nanorods with controlled coupling strength is employed to study the spectral dependence of the plasmon-induced fluorescence enhancement. Perfect matching of the plasmon resonances in the nanorods with the absorption bands of the LH2 complexes facilitates a direct comparison of the enhancement factors for longitudinal and transverse plasmon frequencies of the nanorods. We find that the fluorescence enhancement due to excitation of longitudinal resonance can be up to five-fold stronger than for the transverse one. We attribute this result, which is important for designing plasmonic functional systems, to a very different distribution of the enhancement of the electric field due to the excitation of the two characteristic plasmon modes in nanorods
Modeling Light Trapping in Nanostructured Solar Cells
The integration of nanophotonic and plasmonic structures with solar cells offers the ability to control and confine light in nanoscale dimensions. These nanostructures can be used to couple incident sunlight into both localized and guided modes, enhancing absorption while reducing the quantity of material. Here we use electromagnetic modeling to study the resonances in a solar cell containing both plasmonic metal back contacts and nanostructured semiconductor top contacts, identify the local and guided modes contributing to enhanced absorption, and optimize the design. We then study the role of the different interfaces and show that Al is a viable plasmonic back contact material
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